非アルコール性脂肪肝炎(NASH)治療薬評価における3次元オルガノイド培養法の有用性の検討

抄録

【Backgrounds】

Non-alcoholic steatohepatitis (NASH) is developed the fatty liver in alcohol independence and can progress to cirrhosis or liver cancer in the future. However, there are few therapeutic agents that can improve fibrosis of NASH. Recently, we established NASH liver organoid model reproducing NASH pathology by using a three-dimensional organoid culture method.

【Objects】

In this study, the efficacy of 6 types of therapeutic agents currently used in clinical trials on the fibrosis of NASH liver organoid was evaluated.

【Methods】

7-week-old C57 / BL mice were fed with NASH-induced diet MCD for 12 weeks to prepare advanced fibrosis NASH mice. Then, the liver was extracted to prepare for organoid culture. The 6 therapeutic agents were treated to NASH organoids for one week. The morphological changes of organoids and the expression level of fibrosis markers in liver organoids were evaluated.

【Result and Conclusion】

The morphology of the NASH organoid approached that of the normal liver organoid, and a remarkable morphological change was observed especially in Farnesoid X Receptor (FXR agonists)treated organoids. Besides, the expression of collagen I and a-SMA , which are markers related to fibrosis, was significantly decreased in FXR agonists treated organoids. These results suggest that our established NASH liver organoid model might be useful in the evaluation of the efficacy of therapeutic drug screening for NASH disease.